Researchers observed a significant progression-free survival (PFS) benefit in patients with hormone receptor-positive (HR+), HER2-negative (HER2-) metastatic breast cancer (mBC) who switched to endocrine therapy (ET) plus ribociclib after progression on anti-estrogen therapy plus CDK4/6 inhibition, according to research presented at the 2022 ASCO Annual Meeting.
“While there are observational data supporting the potential benefit of treating with a CDK4/6 inhibitor and switching the endocrine therapy after progression on a CDK4/6 inhibitor, there have been no prospective randomized trials reported with this approach,” said presenter Kevin Kalinsky, MD, of the Winship Cancer Institute at Emory University in Atlanta, Georgia.
Researchers conducted a phase 2, multicenter, randomized trial (MAINTAIN; ClinicalTrials.gov Identifier: NCT02632045) to evaluate the efficacy of fulvestrant or exemestane with or without ribociclib in patients with HR+, HER2- mBC whose cancer previously progressed on a CDK4/6 inhibitor plus ET.
The double-blind trial included men or women with measurable or non-measurable HR+/HER2- mBC. Patients were randomly assigned to receive fulvestrant or exemestane with or without ribociclib. Patients treated with prior fulvestrant received exemestane as ET, and those treated with prior exemestane received fulvestrant as ET. In cases where neither prior fulvestrant or exemestane had been received, fulvestrant (per investigator discretion) was encouraged. The primary endpoint was PFS.
There were 119 randomly assigned and evaluable patients included in the analysis. The median age was 57.0 years, roughly 74% of patients were White, and 1 patient was male.
For ET, 83% of patients received fulvestrant and 17% received exemestane. Prior CDK4/6 inhibitors included palbociclib (~86%), ribociclib (~12%), and abemaciclib (~2%).
The researchers observed a statistically significant PFS improvement in patients randomly assigned to receive fulvestrant or exemestane with ribociclib compared with ET plus placebo. The median PFS was 5.29 months and 2.76 months, respectively (hazard ratio [HR], 0.57; 95% CI, 0.39-0.95; P =.006).
At both 6 and 12 months, the PFS rate was higher in the ribociclib arm than in the placebo arm (6 months, 41.2% vs 23.9%; 12 months, 24.6% vs 7.4%).
Treatment-related adverse events that were more common with ribociclib than with placebo included neutropenia (all grades, 72% vs 15%; grade 3, 38% vs 0%) and thrombocytopenia (all grades, 25% vs 5%).
Anemia was common in both the ribociclib and placebo arms (all grades, 23% vs 22%, respectively). Pneumonitis occurred in 3 patients in the ribociclib arm. Grade 3 infection was reported in 3 patients in the ribociclib arm and 0 patients in the placebo arm.
“This is the first randomized trial to show the benefit of ribociclib and switching endocrine therapy after progression on a CDK4/6 inhibitor,” concluded Dr Kalinsky. “Ribociclib plus endocrine therapy led to a statistically significant improvement in progression-free survival compared to placebo plus endocrine therapy in participants with tumor progression following a CDK4/6 inhibitor.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Kalinsky K, Accordino MK, Chiuzan C, et al. A randomized, phase II trial of fulvestrant or exemestane with or without ribociclib after progression on anti-estrogen therapy plus cyclin-dependent kinase 4/6 inhibition (CDK 4/6i) in patients (pts) with unresectable or hormone receptor–positive (HR+). Presented at ASCO 2022; June 3-7, 2022. Abstract LBA1004.